[unreadable] [unreadable] This project is aimed at evaluating the contribution of mitochondrial haplogroups to breast cancer risk, and any modification of this risk by body mass index (BMI), circulating antioxidant levels, alcohol consumption, or cigarette smoking. This study will use a case-control design nested within the Nurses' Health Study. 1834 breast cancer cases (diagnosed between blood draw in 1989-90 and June 1, 2004) and 3051 matched controls have had DNA extracted and available for use. Eight mitochondrial SNPs will be genotyped to classify the participants into nine common haplogroups. Associations between haplogroups and breast cancer risk will be evaluated using logistic regression. As BMI, circulating antioxidant levels, alcohol consumption, and cigarette smoking have all been hypothesized to increase oxidative stress, modification of any associations between mitochondrial haplogroups and breast cancer risk by these exposures will be evaluated using statistical modeling and likelihood ratio tests. The prospective nature and size of the Nurses' Health Study provide a unique and powerful resource for studying gene and environment interactions. Examining the mitochondrial genome and the interaction between inherited mitochondrial factors and environmental exposures are very novel approaches to breast cancer susceptibility. Any associations observed will provide new and exciting avenues of breast cancer research and treatment, hopefully lowering breast cancer morbidity and mortality. This project will examine a novel breast cancer susceptibility marker, the mitochondrial genome. Mitochondria are the cell's power plant, and as such, generate many toxic substances which are implicated in a wide range of diseases, including cancers. Further understanding of the importance of inherited mitochondrial variation on breast cancer risk will aid future research in screening and treatment to lower the burden of breast cancer, making it very relevant to public health. [unreadable] [unreadable] [unreadable]